It is known that prolylendopeptidase acts on substances P, TRH (thyrotropin releasing hormone) and neurotensin which have been deemed as neural transmitting substance, and vasopressin which is considered to be concerned with memory, and inactivates them. Nakajima et al and Yoshimoto et al found that the compounds which inhibit prolylendopeptidase activity could prevent experimental amnesia in rats induced by scopolamine and presumed that prolylendopeptidase-inhibitory agents were concerned with the consolidation of memory (Nakajima et al, Folia Pharmacologica Japonica, vol. 82, p 154 (1983), Yoshimoto et al, Seikagaku, vol. 55, p 831 (1983)). This suggests a possibility that prolylendopeptidase-inhibitory agents can be used as anti-amnesiac drugs.
Hitherto, as prolylendopeptidase-inhibitory agents, as reported in Japanese Patent Applications Laid-open (Kokai) Nos. 130579/1988 and 162672/1988, known are proline derivatives having a peptide bond.
On the other hand, in Japanese Patent Applications Laid-open (Kokai) Nos. 100765/1981 and 91172/1986 and Journal of Medicinal Chemistry, vol. 8, p 722 (1965), pyridine compounds substituted by a benzoyl group or other groups are reported. Further, anti-anxietic or sedative .omega.-aminoalkoxybenzoylthiophene compounds are disclosed in Japanese Patent Application Laid-open (kokai) No. 56476/1982.
The present inventors have conducted intensive studies for the purpose of developing novel prolylendopeptidase-inhibitory agents in of a non-peptide type.
As the result, the present inventors found novel pyridine derivatives possessing an excellent inhibitory activity on prolylendopeptidases which resulted in the completion of this invention.